Heparin Structure and Interactions with Basic Fibroblast Growth Factor
Abstract
Crystal structures of heparin-derived tetra- and hexasaccharides complexed with basic fibroblast growth factor (bFGF) were determined at resolutions of 1.9 and 2.2 angstroms, respectively. The heparin structure may be approximated as a helical polymer with a disaccharide rotation of 174° and a translation of 8.6 angstroms along the helix axis. Both molecules bound similarly to a region of the bFGF surface containing residues asparagine-28, arginine-121, lysine-126, and glutamine-135; the hexasaccharide also interacted with an additional binding site formed by lysine-27, asparagine-102, and lysine-136. No significant conformational change in bFGF occurred upon heparin oligosaccharide binding, which suggests that heparin primarily serves to juxtapose components of the FGF signal transduction pathway.
Additional Information
© 1996 American Association for the Advancement of Science. 19 September 1995; Accepted 12 December 1995. We thank T. Arakawa and G. M. Fox of Amgen for discussions and a generous supply of bFGF and D. Bar-Shalom for stimulating conversations. This work was funded in part by a gift from Amgen and U.S. Public Health Service (USPHS) grant GM38060(R.J.L.), with partial support of the x-ray facility provided by the Beckman Institute at California Institute of Technology and USPHS grant GM45162 (D.C.R.). S.F. was supported by USPHS Biotechnology Training grant T32 GM08346.Additional details
- Eprint ID
- 53136
- DOI
- 10.1126/science.271.5252.1116
- Resolver ID
- CaltechAUTHORS:20141223-090448077
- Amgen
- U.S. Public Health Service (USPHS)
- GM38060
- Caltech Beckman Institute
- NIH
- GM45162
- NIH
- T32 GM08346
- Created
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2014-12-23Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field